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Multiple sclerosis and the TNFRSF1A R92Q mutation: clinical characteristics of 21 cases.
Neurology 2008; 71(22):1812-20Neur

Abstract

OBJECTIVE

Tumor necrosis factor receptor 1-associated periodic syndrome (TRAPS) is an autosomal dominantly inherited autoinflammatory disorder resulting from mutations in the TNFRSF1A gene, which encodes the p55 receptor for tumor necrosis factor alpha. We recently identified the R92Q mutation encoded by exon 4 in six patients with multiple sclerosis (MS) who reported at least two symptoms suggestive of TRAPS. The current study presents the characteristics of a larger cohort of MS patients carrying this mutation.

METHODS

Clinical and laboratory parameters, including human leukocyte antigen (HLA)-DR15 status, were evaluated, and genetic testing was performed. Whenever possible, family members were also invited for interview and mutation analysis.

RESULTS

Twenty TNFRSF1A R92Q carriers had MS according to the McDonald criteria, and 1 had clinically isolated syndrome. The majority of patients had typical onset and features of MS. Nine patients carried an HLA-DR15 haplotype. All individuals showed TRAPS-compatible symptoms, which consisted mainly of myalgias, arthralgias, headache, severe fatigue, and skin rashes; were milder than usually described; and appeared mainly in adulthood. Most patients experienced severe side effects during immunomodulatory therapy for MS. Seventeen family members carried the identical mutation, and 15 of them reported symptoms suggestive of TRAPS.

CONCLUSION

In most cases with multiple sclerosis (MS) and coexisting tumor necrosis factor receptor 1-associated periodic syndrome (TRAPS), features of MS were quite typical, whereas TRAPS presented mostly without the fever episodes observed in childhood. The penetrance of the R92Q mutation in affected family members was higher than reported. We recommend careful observation of MS patients with coexisting TRAPS with regard to unexpected side effects of immunomodulatory therapies.

Authors+Show Affiliations

Institute of Clinical Neuroimmunology-Grosshadern, Ludwig Maximilians University of Munich, Munich, Germany. tania.kuempfel@med.uni-muenchen.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19029521

Citation

Kümpfel, T, et al. "Multiple Sclerosis and the TNFRSF1A R92Q Mutation: Clinical Characteristics of 21 Cases." Neurology, vol. 71, no. 22, 2008, pp. 1812-20.
Kümpfel T, Hoffmann LA, Pellkofer H, et al. Multiple sclerosis and the TNFRSF1A R92Q mutation: clinical characteristics of 21 cases. Neurology. 2008;71(22):1812-20.
Kümpfel, T., Hoffmann, L. A., Pellkofer, H., Pöllmann, W., Feneberg, W., Hohlfeld, R., & Lohse, P. (2008). Multiple sclerosis and the TNFRSF1A R92Q mutation: clinical characteristics of 21 cases. Neurology, 71(22), pp. 1812-20. doi:10.1212/01.wnl.0000335930.18776.47.
Kümpfel T, et al. Multiple Sclerosis and the TNFRSF1A R92Q Mutation: Clinical Characteristics of 21 Cases. Neurology. 2008 Nov 25;71(22):1812-20. PubMed PMID: 19029521.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple sclerosis and the TNFRSF1A R92Q mutation: clinical characteristics of 21 cases. AU - Kümpfel,T, AU - Hoffmann,L-A, AU - Pellkofer,H, AU - Pöllmann,W, AU - Feneberg,W, AU - Hohlfeld,R, AU - Lohse,P, PY - 2008/11/26/pubmed PY - 2008/12/19/medline PY - 2008/11/26/entrez SP - 1812 EP - 20 JF - Neurology JO - Neurology VL - 71 IS - 22 N2 - OBJECTIVE: Tumor necrosis factor receptor 1-associated periodic syndrome (TRAPS) is an autosomal dominantly inherited autoinflammatory disorder resulting from mutations in the TNFRSF1A gene, which encodes the p55 receptor for tumor necrosis factor alpha. We recently identified the R92Q mutation encoded by exon 4 in six patients with multiple sclerosis (MS) who reported at least two symptoms suggestive of TRAPS. The current study presents the characteristics of a larger cohort of MS patients carrying this mutation. METHODS: Clinical and laboratory parameters, including human leukocyte antigen (HLA)-DR15 status, were evaluated, and genetic testing was performed. Whenever possible, family members were also invited for interview and mutation analysis. RESULTS: Twenty TNFRSF1A R92Q carriers had MS according to the McDonald criteria, and 1 had clinically isolated syndrome. The majority of patients had typical onset and features of MS. Nine patients carried an HLA-DR15 haplotype. All individuals showed TRAPS-compatible symptoms, which consisted mainly of myalgias, arthralgias, headache, severe fatigue, and skin rashes; were milder than usually described; and appeared mainly in adulthood. Most patients experienced severe side effects during immunomodulatory therapy for MS. Seventeen family members carried the identical mutation, and 15 of them reported symptoms suggestive of TRAPS. CONCLUSION: In most cases with multiple sclerosis (MS) and coexisting tumor necrosis factor receptor 1-associated periodic syndrome (TRAPS), features of MS were quite typical, whereas TRAPS presented mostly without the fever episodes observed in childhood. The penetrance of the R92Q mutation in affected family members was higher than reported. We recommend careful observation of MS patients with coexisting TRAPS with regard to unexpected side effects of immunomodulatory therapies. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/19029521/Multiple_sclerosis_and_the_TNFRSF1A_R92Q_mutation:_clinical_characteristics_of_21_cases_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=19029521 DB - PRIME DP - Unbound Medicine ER -